Hypoxia promotes bone marrow-derived mesenchymal stem cell proliferation through apelin/APJ/autophagy pathway

Lanfang Li,  Lifang Li,  Zidong Zhang and  Zhisheng Jiang

Post-doctoral Mobile Stations for Basic Medicine, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, China  

Acta Biochim Biophys Sin 2015, 47: 362–367; doi: 10.1093/abbs/gmv014

Bone marrow-derived mesenchymal stem cells (BMSCs) are a population of multipotent progenitors that have the capacity of proliferation and differentiation into mesenchymal lineage cells. The regulatory peptide apelin is the endogenous ligand for the G protein-coupled receptor APJ. Apelin, which can enhance BMSC proliferation, has mitogenic effects on a wide variety of cell types. We hypothesized that the increased apelin/APJ might be involved in the occurrence and development of hypoxia-induced BMSC proliferation. BMSCs from the bone marrow of 8- to 10-week-old C57BL/6J mice were cultured under either normoxia (21% oxygen) or hypoxia (1% oxygen) condition. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-bromo-2′-deoxyuridine assay. Expressions of hypoxia-inducible factor (HIF)-1α, apelin, APJ, Beclin-1, and LC3II/LC3I were detected by western blot analysis. Results suggested that hypoxia enhanced the proliferation of BMSC in a time-dependent manner. The expressions of HIF-1α, apelin, APJ, Beclin-1, and LC3II/LC3I were increased in BMSCs induced by hypoxia. Small interfering RNA (siRNA)-HIF-1α that inhibited the hypoxia-induced expressions of apelin, APJ, Beclin-1, and LC3II/LC3I prevented hypoxia-induced BMSC proliferation. siRNA-APJ that inhibited the hypoxia-induced expressions of Beclin-1 and LC3II/LC3I reversed hypoxia-induced BMSC proliferation. siRNA-Beclin-1 also abolished hypoxia-induced cell proliferation. These data suggested that the apelin/APJ/autophagy signaling pathway might be involved in hypoxia-induced BMSC proliferation.

HIF-1α, apelin, APJ, Beclin-1, and LC3II/LC3I increase in BMSCs induced by hypoxia

全文: http://abbs.oxfordjournals.org/content/47/5/362.full

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